Drug Survival of IL-12/23, IL-17 and IL-23 Inhibitors for Psoriasis Treatment: A Retrospective Multi-Country, Multicentric Cohort Study

Torres, Tiago; Puig, Luís; Vender, Ronald; Lynde, Charles; Piaserico, Stefano; Carrascosa, J.M.; Gisondi, Paolo; Daudén, E.; Conrad, Curdin; Mendes‐Bastos, Pedro; Ferreira, Paulo; Leite, Luíz; Lu, Justin D.; Valério, Joana; Bruni, Manfredo; Messina, Francesco; Nidegger, Alessia; Llamas‐Velasco, M.; Alcázar, E. del; Mufti, Asfandyar; White, Kyra; Caldarola, Giacomo; Teixeira, Laetitia; Romanelli, Paolo; Desai, K.; Gkalpakiotis, Spyridon; Romanelli, Marco; Yeung, Jensen; Nogueira, Miguel; Chiricozzi, Andrea

doi:10.1007/s40257-021-00598-4

Cited by 77 publications

(116 citation statements)

References 33 publications

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“…Although not universally confirmed, but consistent with most of the previous RWE studies, we have found that patients who presented obesity [5,14] or were previously exposed to biologic treatments (versus naı ¨ve patients) [3-5, 7, 10, 11, 14-16] showed an increased risk of discontinuing SEC. Moreover, in our study, patients who received two or more biologicals with different mechanisms of action before SEC discontinued treatment before naı ¨ve patients.…”

Section: Discussionsupporting

confidence: 90%

“…Interestingly, no significant difference was found regarding drug survival rates between the group of patients who started with baseline PASI C 10 and those who started with PASI \ 10, which is commonly overlooked in other drug survival studies in a real-world setting. On the other hand, in several studies it has been observed that the female gender was significantly associated with a poorer persistence [3,12,14,15]. This was not observed in our cohort of patients or in other studies [4,5].…”

Section: Discussioncontrasting

confidence: 75%

“…Although some real-world evidence (RWE) studies reporting the rates of S-SEC in psoriasis patients are available [2][3][4][5][6][7][8][9][10][11][12][13][14][15], scarce evidence about survival C 2 years has been collected [16][17][18][19][20]. In most of the RWE studies included in two meta-analyses [6,13], the patients were followed for a period shorter than 1 year.…”

Section: Discussionmentioning

confidence: 99%

“…Secukinumab (SEC) is a fully human monoclonal IgG1/j isotype antibody that selectively binds to and neutralizes interleukin 17A (IL-17A), a proinflammatory cytokine with key involvement in the clinical manifestation of psoriasis [1]. Despite its high effectiveness and safety profile demonstrated in the treatment of moderateto-severe plaque psoriasis, there is limited and conflicting evidence over the real-world drug survival of secukinumab in patients with psoriasis [2][3][4][5][6][7][8][9][10][11][12][13][14][15], especially in the long term [16][17][18]. Moreover, there is also a great variability in the results related to the predictors of a greater or lesser survival.…”

Section: Introductionmentioning

confidence: 99%

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Multicenter Retrospective Study of Secukinumab Drug Survival in Psoriasis Patients in a Daily Practice Setting: A Long-Term Experience in Spain

Daudén

Lima

Armesto

et al. 2021

Dermatol Ther (Heidelb)

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Introduction: There is limited and conflicting evidence over the real-world drug survival of secukinumab (SEC) in patients with psoriasis, especially in the long term. Our objective was to analyze the short-and long-term survival of SEC (S-SEC) and its predictive factors for the treatment of psoriasis. Methods: Patients clinically diagnosed with plaque psoriasis and under treatment with secukinumab (n = 384) in a daily practice setting were analyzed in a retrospective, multicenter study performed in a nationwide cohort and followed up for a period of 2 years. Kaplan-Meier curve was plotted to analyze drug E. Daude ´n (&) Á G.

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Section: Discussionsupporting

confidence: 90%

Section: Discussioncontrasting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multicenter Retrospective Study of Secukinumab Drug Survival in Psoriasis Patients in a Daily Practice Setting: A Long-Term Experience in Spain

Daudén

Lima

Armesto

et al. 2021

Dermatol Ther (Heidelb)

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“…In a recent study, Blauvelt et al compared the overall survival of ixekizumab and adalimumab with results similar to our drug survival analysis, although the impact of BMI on these results was not analyzed [41]. Therefore, our findings highlight an unexpected result, showing a greater influence of high BMI values on the efficacy of anti-IL drugs when compared with anti-TNF drugs, with worse performances in obese patients, in line with the negative impact of BMI on the efficacy and drug survival of anti-IL drugs reported in recent studies [42][43][44]. Our results might be explained by the inflammatory background of obese patients, in which TNFα is the most represented inflammatory mediator, owing to its release from adipose tissue under the influence of resistin.…”

Section: Discussionsupporting

confidence: 79%

Impact of Body Mass Index on the Efficacy of Biological Therapies in Patients with Psoriasis: A Real-World Study

et al. 2021

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Background The efficacy of biological therapies used for the treatment of chronic plaque psoriasis can be influenced by numerous variables including body mass index (BMI). Objective This study aimed to evaluate the impact of BMI on the short-term and long-term efficacy of biological therapies in clinical practice and to identify the best therapeutic options in obese patients (BMI ≥ 30 kg/m 2 ). Methods A multicentric retrospective study was conducted in patients who initiated a biological therapy during the period January 2006-December 2019. The proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index at weeks 12 and 24 was calculated also recording the 12-and 24-month drug survival as a measure of longterm efficacy, performing multivariate analyses to assess the impact of different variables. Results Five hundred and four patients with psoriasis were included. After 12 and 24 weeks, the proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index response was higher in patients with a BMI < 30 kg/m 2 compared with those with a BMI ≥ 30 kg/m 2 [54.90% vs 43.45% (p = 0.014) at week 12 and 66.84% vs 56.55% (p = 0.021) at week 24]. The Kaplan-Meier survival curves showed how obese patients had a higher probability of discontinuation due to a lack or loss of efficacy (p = 0.0192) compared with non-obese patients. The drug survival analysis also showed that BMI negatively affected the drug survival of secukinumab (odds ratio 1.27, p < 0.001) and ustekinumab (odds ratio 1.06, p = 0.050), while the long-term efficacy of adalimumab, etanercept, and ixekizumab was not influenced by BMI. Conclusions Obesity (BMI ≥ 30 kg/m 2 ) negatively affects the clinical response of biological drugs in psoriatic patients, with anti-interleukin drugs being more affected by BMI than anti-tumor necrosis factor drugs. Key PointsOur results highlight the importance of considering patient-related and disease-related variables when choosing the most appropriate treatment for each subject affected by psoriasis.Obesity can negatively affect the short-term and longterm efficacy of biological therapies.In our analysis, anti-interleukin drugs seem to be more affected by a patient's weight than anti-tumor necrosis factor drugs.

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Targeting Immune Checkpoints and Cytokines to Protect From Psoriasis Relapse

Ghoreschi

2021

JAMA Dermatol

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In contrast to the state of the field 10 years ago, the understanding of disease pathogenesis and the treatment goals for patients with psoriasis have changed enormously. A 75% improvement in the Psoriasis Area and Severity Index (PASI 75) is no longer the desirable treatment goal for dermatologists or for disease-experienced patients with plaque-type psoriasis. Physicians and patients now demand a PASI 90 or even a PASI 100. Identification of interleukin (IL)-17 and IL-23 as key mediators in the pathogenesis of psoriasis and the development of new biologics that target these pathways are major steps toward disease control. 1 By targeting cytokines, a clear or almost clear disease status became an achievable goal in a substantial number of patients. The molecular and cellular mechanisms that underlie disease milestones in psoriasis treatment have not yet been fully elucidated, and we remain far from a permanent cure. In particular, we are missing the biomarkers and molecular indicators of forthcoming psoriasis flares in patients who show no or minimal disease activity. This is critical information for identifying the appropriate point in time to discontinue a systemic medication in an individual who has achieved disease control.What has changed since the introduction of tumor necrosis factor blockers as successful biologics for psoriasis? Research in dermatology uncovered the immunopathology of psoriasis and unveiled psoriasis as the prototypic subtype 17 helper T cell (Th17)-mediated autoimmune disease in humans, with IL-17-and IL-22-producing T cells being key inflammatory mediators. 1 Contrary to our thinking at the beginning of this millennium, Th1 cells and interferons seem to be less important in psoriatic skin inflammation. 2 Cytokines are responsible for many results in psoriasis, including altered proliferation and activation of keratinocytes and endothelia. IL-17A together with IL-22 and tumor necrosis factor regulate the secretion of factors like antimicrobial peptides (eg, human β-defensin 2) or epithelial mediators (eg,.The most critical factor for Th17-dependent autoimmune disease, however, is IL-23. Although IL-17A expression can occur in the absence of IL-23, the phenotype and pathogenicity of IL-23-generated Th17 cells are different. 3 In psoriasis, monoclonal antibodies (mAbs) that are directed against IL-17A, IL-17RA, or IL-17A/F but also neutralization of IL-23 all show high efficacy. 1 Interleukin 23 is composed of 2 units, p19 and p40. The latter unit, together with p35, forms IL-12. A mAb that is directed toward IL-12/IL-23p40 (ustekinumab) was introduced years before mAbs against IL-17A or IL-23p19 were approved. Data from indirect comparison and head-to-head

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Drug Survival of IL-12/23, IL-17 and IL-23 Inhibitors for Psoriasis Treatment: A Retrospective Multi-Country, Multicentric Cohort Study

Cited by 77 publications

References 33 publications

Multicenter Retrospective Study of Secukinumab Drug Survival in Psoriasis Patients in a Daily Practice Setting: A Long-Term Experience in Spain

Multicenter Retrospective Study of Secukinumab Drug Survival in Psoriasis Patients in a Daily Practice Setting: A Long-Term Experience in Spain

Impact of Body Mass Index on the Efficacy of Biological Therapies in Patients with Psoriasis: A Real-World Study

Targeting Immune Checkpoints and Cytokines to Protect From Psoriasis Relapse

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